This proposal has 3 main objectives, all of them related to the genetics of the ciliate, Tetrahymena pyriformis: a) To gain further insights into the basic genetics of the macronucleus; b) To understand better and improve methods of isolation of mutants for the purpose of carrying out genetic dissection; and c) To isolate a variety of mutants related to the nutrition of Tetrahymena. The first objective will be important in illuminating genetic phenomena of general interest related to the expression, distribution and recombination of macronuclear genetic information. The second objective will help to develop further the potential of Tetrahymena as an animal model system in which biological problems of interest can be attacked by genetic dissection. The third objective will yield a variety of mutants useful for further genetic work and for better understanding of nutrient transport and lysosome enzyme synthesis and release. The utility of being able to use Tetrahymena for genetic dissection goes beyond the study of Tetrahymena. There are few (if any) other animal cells which combine the facility of doing both genetics and biochemistry which Tetrahymena has. Consequently, this organism has the potential of becoming a model system for animal cells, by providing a versatile experimental system in which problems of general significance to cell biology can be readily approached at the molecular level. Given the universality of the molecular basis of many cellular mechanisms, the concepts and methods derived from this system should have applicability to many health-related problems, such as the biology of disease-causing eucaryotic organisms, developmental problems (cancer and aging, for example) and "molecular" diseases.